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Molecular modeling and characterization of Vibrio cholerae transcription regulator HlyU.

ABSTRACT: BACKGROUND: The SmtB/ArsR family of prokaryotic metal-regulatory transcriptional repressors represses the expression of operons linked to stress-inducing concentrations of heavy metal ions, while derepression results from direct binding of metal ions by these 'metal-sensor' proteins. The HlyU protein from Vibrio cholerae is the positive regulator of haemolysin gene, it also plays important role in the regulation of expression of the virulence genes. Despite the understanding of biochemical properties, its structure and relationship to other protein families remain unknown. RESULTS: We find that HlyU exhibits structural features common to the SmtB/ArsR family of transcriptional repressors. Analysis of the modeled structure of HlyU reveals that it does not have the key metal-sensing residues which are unique to the SmtB/ArsR family of repressors, yet the tertiary structure is very similar to the family members. HlyU is the only member that has a positive control on transcription, while all the other members in the family are repressors. An evolutionary analysis with other SmtB/ArsR family members suggests that during evolution HlyU probably occurred by gene duplication and mutational events that led to the emergence of this protein from ancestral transcriptional repressor by the loss of the metal-binding sites. CONCLUSION: The study indicates that the same protein family can contain both the positive regulator of transcription and repressors--the exact function being controlled by the absence or the presence of metal-binding sites.

SUBMITTER: Saha RP

PROVIDER: S-EPMC1665450 | biostudies-literature | 2006

REPOSITORIES: biostudies-literature

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Molecular modeling and characterization of Vibrio cholerae transcription regulator HlyU.

Saha Rudra P RP Chakrabarti Pinak P

BMC structural biology 20061120

<h4>Background</h4>The SmtB/ArsR family of prokaryotic metal-regulatory transcriptional repressors represses the expression of operons linked to stress-inducing concentrations of heavy metal ions, while derepression results from direct binding of metal ions by these 'metal-sensor' proteins. The HlyU protein from Vibrio cholerae is the positive regulator of haemolysin gene, it also plays important role in the regulation of expression of the virulence genes. Despite the understanding of biochemica ...[more]

PMID: 17116251

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Project description:Toxigenic Vibrio cholerae serogroup O1 is the etiologic agent of the disease cholera, and strains of this serogroup are responsible for pandemics. A few other serogroups have been found to carry cholera toxin genes-most notably, O139, O75, and O141-and public health surveillance in the United States is focused on these four serogroups. A toxigenic isolate was recovered from a case of vibriosis from Texas in 2008. This isolate did not agglutinate with any of the four different serogroups' antisera (O1, O139, O75, or O141) routinely used in phenotypic testing and did not display a rough phenotype. We investigated several hypotheses that might explain the recovery of this potential nonagglutinating (NAG) strain using whole-genome sequencing analysis and phylogenetic methods. The NAG strain formed a monophyletic cluster with O141 strains in a whole-genome phylogeny. Furthermore, a phylogeny of ctxAB and tcpA sequences revealed that the sequences from the NAG strain also formed a monophyletic cluster with toxigenic U.S. Gulf Coast (USGC) strains (O1, O75, and O141) that were recovered from vibriosis cases associated with exposures to Gulf Coast waters. A comparison of the NAG whole-genome sequence showed that the O-antigen-determining region of the NAG strain was closely related to those of O141 strains, and specific mutations were likely responsible for the inability to agglutinate. This work shows the utility of whole-genome sequence analysis tools for characterization of an atypical clinical isolate of V. cholerae originating from a USGC state. IMPORTANCE Clinical cases of vibriosis are on the rise due to climate events and ocean warming (1, 2), and increased surveillance of toxigenic Vibrio cholerae strains is now more crucial than ever. While traditional phenotyping using antisera against O1 and O139 is useful for monitoring currently circulating strains with pandemic or epidemic potential, reagents are limited for non-O1/non-O139 strains. With the increased use of next-generation sequencing technologies, analysis of less well-characterized strains and O-antigen regions is possible. The framework for advanced molecular analysis of O-antigen-determining regions presented herein will be useful in the absence of reagents for serotyping. Furthermore, molecular analyses based on whole-genome sequence data and using phylogenetic methods will help characterize both historical and novel strains of clinical importance. Closely monitoring emerging mutations and trends will improve our understanding of the epidemic potential of Vibrio cholerae to anticipate and rapidly respond to future public health emergencies.

Dataset Information

Molecular modeling and characterization of Vibrio cholerae transcription regulator HlyU.

Publications

Molecular modeling and characterization of Vibrio cholerae transcription regulator HlyU.

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